tbuckley/cabot-search huggingface dataset:
Survival outcomes of pulmonary metastasectomy in advanced melanoma patients: An inverse probability weighted analysis.
Authors: Sebawe Syaj, Marah Akhdar, Osaid Alser, Mohamedraed Elshami, Shadi Hamouri
Journal: Journal of Clinical Oncology (2022)

e21518 Background: Pulmonary metastasectomy (PM) is a commonly performed procedure for certain patients with lung metastasis. We aimed to estimate the effect of PM on the survival outcomes of advanced melanoma patients with lung metastasis. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database for all adult patients with advanced melanoma (AYA site recode) with lung metastasis (Stage M1b according to AJCC 7 th edition) who were diagnosed from 2010 to 2015. Patients with known liver, brain, or bone metastasis were excluded. Our primary outcomes were overall survival (OS) and cancer-specific survival (CSS) in months. We used Kaplan-Meier plots to compare survival outcomes between treatment groups. We adjusted for potential confounders including age, sex, marital status, primary tumor surgery, chemotherapy, and radiotherapy in a multivariate analysis. We carried out an inverse probability (IP)-weighted Cox regression in an attempt to eliminate the effect of nonrandomization when estimating the treatment effect of PM on OS and CSS. Results: We included 520 patients; 98 (18.8%) underwent PM and 422 (81.2%) did not. The sample median age was 71 (IQR: 61-80). T0 stage was prevalent in 179 (34.4%) and N0-1 in 302 (58.1%). Primary surgical resection was performed for 217 (41.7%) patients, 136 (26.2%) patients had undergone chemotherapy, and radiotherapy was administered in 64 (12.3%) patients. Patients who underwent PM had a higher median OS than patients who did not (43.0 months, 95% CI: 25.0-not reached vs. 13 months, 95% CI: 11-16). The median CSS in PM group patients was not reached (95% CI: 43.0-not reached), while it was 16 months (95% CI: 13-21) in non-PM patients. After multivariate adjustment, older age, being single, and not undergoing primary surgical resection, were all significant independent prognostic factors for worse OS and CSS. In contrast, sex and receipt of chemotherapy and/or radiotherapy did not affect either OS or CSS. PM group patients had a significant survival advantage than non-PM patients, in terms of OS and CSS (HR = 0.50, 95% CI: 0.37-0.67 and HR = 0.45, 95% CI: 0.32-0.63, respectively). On the IP-weighted Cox analysis, the survival benefits of PM were still significantly favorable for OS (IP-weighted HR = 0.42, 95% CI: 0.30-0.59) and CSS (IP-weighted HR = 0.38, 95% CI: 0.26-0.57). Conclusions: PM in a multimodality treatment setting resulted in a marked survival advantage for patients with advanced melanoma who had lung metastasis only. The management of such patients should be delicately individualized to optimize their survival outcomes.
MEDB-24. Tumour secreted extracellular matrix predicts survival and influences migration and cell death in SHH medulloblastoma 3D models
Authors: James Johnson, Franziska Linke, Cathy Merry, Beth Coyle
Journal: Neuro-Oncology (2022)

Abstract Medulloblastoma is the most common malignant paediatric brain tumour. Four molecular sub-groups exist (WNT, Sonic hedgehog (SHH), Group 3 and Group 4), each associated with different patterns of metastasis and chemoresistance. We have shown that within these sub-groups further clinically relevant sub-types exist, characterised by differential expression of extracellular matrix (ECM) proteins. For example, good overall survival in two-thirds of SHH sub-group patients is associated with the expression of specific ECM proteins. Our aim here is to further characterise these ECM components in SHH medulloblastoma and to determine how they confer better overall survival in this sub-group. Using a combination of 3D OrbiSIMs and immunohistochemical staining we have identified, that when grown in 3D hyaluronic acid hydrogels or as spheroids, SHH medulloblastoma cell lines form an ECM shell-like structure composed of laminin, collagen and lumican. In addition, scRNAseq of SHH hydrogel nodules revealed sub-group specific clusters of cells with high levels of ECM interaction and adhesion. We therefore hypothesise that ECM interaction restricts SHH tumour invasion and metastasis through this shell-like structure. To understand how this ECM shell-like structure potentiates better survival in SHH medulloblastoma we have created a CRISPRcas9 laminin knockout SHH medulloblastoma cell line. 3D culture of the laminin knockout cell line demonstrated that laminin is essential for the formation of 3D cell structures as well as migration in SHH medulloblastoma. Furthermore, we have identified that apoptosis is increased in the laminin knockout SHH cell line, suggesting that apoptosis-targeted therapeutics may represent a beneficial treatment option for SHH patients whose tumours exhibit this ECM shell. In summary, tumour-secreted ECM plays a major role in SHH medulloblastoma progression. Expression of laminin, collagen or lumican can be used to classify SHH patients into low and high-risk groups with different therapeutic outcomes and treatment options.
RARE-30. Novel collision tumor of craniopharyngioma and ependymoma in a pediatric patient: a case study
Authors: Rachel Gray, Franklin Chien, Jose Velazquez Vega, Brooke Patteson, David Wrubel, Bree Eaton, Matthew Schniederjan, Claire Mazewski
Journal: Neuro-Oncology (2022)

Abstract Collision tumors are rare tumors comprised of two distinct histologies. In this case report, we discuss a suprasellar collision tumor consisting of adamantinomatous craniopharyngioma and supratentorial ependymoma in a pediatric patient. Case Presentation: Our patient was a two-year-old female with progressive craniopharyngioma status post cyst decompression with Ommaya reservoir placement, subcutaneous peginterferon, Ommaya taps, and subtotal resection. An MRI three months post-resection showed progression and treatment was started with subcutaneous interferon alfa. After eight weeks, she presented with new onset headaches and vomiting. MRI demonstrated tumor progression with associated obstructive hydrocephalus. She underwent a subtotal resection. Pathology revealed recurrent adamantinomatous craniopharyngioma and a 0.5cm ependymoma with classic histomorphology lacking anaplasia features. The ependymoma was positive for GFAP immunostain and EMA immunohistochemistry highlighted a ‘dot-like’ reaction. The Ki-67 proliferation index was very low (&amp;lt;1%). The limited diagnostic material precluded further genomic characterization of the ependymoma. The previous pathology was reviewed and no ependymoma was identified. Spine MRI was negative for metastatic disease. CSF cytology was negative for malignant cells. Following recovery from surgery, she received 54Gy (RBE) focal proton radiation. Eight months from completion of therapy, surveillance MRI shows stable residual tumor. Genetic work-up for cancer predisposition syndrome is in process despite no strong family history of cancer. Discussion: Due to the patient’s young age at diagnosis, our initial treatment strategy was to delay radiotherapy and utilize other treatment options. Following diagnosis with a collision tumor, the patient proceeded to radiotherapy to manage both tumor components. The role of interferon in the development of a collision tumor in this patient in unknown, but we suspect it to be unrelated. Conclusion: To our knowledge, this is the first documented case of a suprasellar collision tumor comprised of craniopharyngioma and ependymoma. Discovery of the collision tumor impacted the patient’s treatment plan.
Drop-out rates from active surveillance for disease progression remain consistent and not negligible over time. A plea for long-term assessment based on a large, prospectively collected active surveillance cohort
Authors: L. Nocera, R. Leni, A. Stabile, G. Gandaglia, V. Cucchiara, G. Rosiello, G. Sorce, F. Pellegrino, S. Scuderi, F. Barletta, A. Gallina, N. Fossati, E. Zaffuto, M. Moschini, N. Suardi, S. Shariat, F. Montorsi, A. Briganti
Journal: European Urology (2022)
Prompting endogenous repair of brain injury: science fiction or reality?
Authors: Aurelie de Rus Jacquet, Francesca Cicchetti
Journal: Molecular Neurodegeneration (2022)

Abstract Drug-refractory forms of neurological diseases could find their next breakthrough therapy in non-pharmacological approaches to brain repair. Lentini et al. present the potential of in situ brain regeneration to address neurodegeneration in the epileptic brain.
ETMR-06. Molecular and clinical characteristics of CNS tumors with<i>BCOR(L1</i>) fusion/internal tandem duplication
Authors: Johannes Gojo, Felix Schmitt-Hoffner, Monika Mauermann, Katja von Hoff, Martin Sill, Andrey Korshunov, Damian Stichel, David Capper, Arnault Tauziede-Espariat, Pascale Varlet, Kenneth Aldape, Zied Abdullaev, Andrew Donson, Jens Pahnke, Ulrich Schüller, Ivy Tran, Kristyn Galbraith, Matija Snuderl, Sanda Alexandrescu, Sebastian Brandner, Maria Łastowska, Evelina Miele, Jasper v Lugt, Lisethe Meijer, Jens Bunt, Christof Kramm, Jordan R Hansford, Lenka Krskova, Michal Zapotocky, Sumihito Nobusawa, David Solomon, Christine Haberler, Barbara Jones, Dominik Sturm, Felix Sahm, Natalie Jäger, Stefan M Pfister, Marcel Kool
Journal: Neuro-Oncology (2022)

Abstract Central nervous system (CNS) tumor with BCOR internal tandem duplication (BCOR-ITD) have recently been introduced in the 5th edition of the WHO classification of CNS tumors, however, their molecular makeup and clinical characteristics remain widely enigmatic. This is further complicated by the recent discovery of tumors characterized by gene fusions involving BCOR or its homologue BCORL1. We identified a cohort of 206 BCOR altered CNS tumors via DNA methylation profiling and conducted in-depth molecular and clinical characterization in an international effort. By performing t-SNE clustering analysis we found that BCOR-fusion tumors form a distinct cluster (n=61), adjacent to BCOR-ITD cases (n=145). The identified fusion partners of BCOR(L1) included EP300 (n=20), CREBBP (n=5), and NUTM2HP (n=1). Notably, three cases within the BCOR-ITD cluster harbored a c-terminal intragenic deletion within BCOR. With respect to clinical characteristics gender ratio was balanced in BCOR-fusion cases (m/f, 1.1), whereas predominance of male patients was observed in the BCOR-ITD group (m/f, 1.5). Moreover, age at diagnosis of BCOR-fusion patients was higher as compared to BCOR-ITD cases (15 vs 4.5 years). Interestingly, BCOR-fusion tumors were exclusively found in the supratentorial region being originally diagnosed as ependymomas or gliomas whereas BCOR-ITD emerged across the entire CNS with diverse original diagnoses. 8% of BCOR-ITD and none of BCOR-fusion cases were disseminated at diagnosis. In line with this observation, 40% of first relapses within the BCOR-ITD group were metastatic which was less frequent in BCOR-fusion tumors. Survival estimates demonstrated no differences, generally showing short median PFS (BCOR-fusion, 2 years, n=15; BCOR-ITD, 1.8 years, n=55) and intermediate OS rates (BCOR-fusion, 6.8 years, n=18; BCOR-ITD 6.3 years, n=60). Further molecular and clinical characterization is ongoing potentially revealing first therapeutic leads for these highly aggressive CNS tumor types.
Correction: The Impact of Vaccination on Incidence and Outcomes of SARS-CoV-2 Infection in Patients with Kidney Failure in Scotland
Journal: Journal of the American Society of Nephrology (2022)

Samira Bell, Jacqueline Campbell, Emilie Lambourg, Chrissie Watters, Martin O’Neil, Alison Almond, Katharine Buck, Edward J. Carr, Laura Clark, Zoe Cousland, Mark Findlay, Nicola Joss, Wendy Metcalfe, Michaela Petrie, Elaine Spalding, Jamie P. Traynor, Vinod Sanu, Peter Thomson, Shona Methven,
RARE-02. Craniopharyngiomas diagnosed as incidentalomas - results of KRANIOPHARYNGEOM 2007
Authors: Svenja Boekhoff, Brigitte Bison, Maria Eveslage, Panjarat Sowithayasakul, Hermann L Müller
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: Childhood-onset craniopharyngiomas (CP) are diagnosed due to clinical symptoms (symCP) or incidentally (incCP). We investigated clinical manifestations and outcome in incCPs and symCPs. METHODS: IncCP were discovered in 4 (3m / 1f) and symCP in 214 (101m / 113f) CP recruited 2007–2014 in KRANIOPHARYNGEOM 2007. Age, sex, height, body mass index (BMI), tumor volume, degree of resection, pre- and postsurgical hypothalamic involvement/lesions, pituitary function and outcome were compared between both subgroups. RESULTS: Reasons for imaging in incCP were cerebral palsy, head trauma, nasal obstruction, and tethered-cord syndrome, whereas headache (44%), visual impairment (25%), and growth retardation (17%) lead to imaging in symCP. Tumor volume at diagnosis was smaller in incCP (median 2.39 cm3; range: 0.14 – 4.10 cm3) when compared with symCP (15.86 cm3; 0.002 – 286.34 cm3). Age, gender, BMI, height, hydrocephalus, tumor location, and hypothalamic involvement at diagnosis of incCP were within the range of these parameters in symCP. Complete resections were achieved more frequently (3/4 patients) in incCP when compared with symCP (20%). Surgical hypothalamic lesions were distributed similar in incCP and symCP. Irradiation was performed only in symCP (33%). No noticeable differences were observed concerning survival rates, endocrine deficiencies, BMI, height, functional capacity and quality of life of the 4 incCP cases when compared with the symCP cohort. CONCLUSIONS: IncCP are rare (1.8%) and characterized by lack of endocrine deficiencies, resulting in normal height and BMI, no hydrocephalus, and smaller tumor volume at diagnosis when compared with symCPs. Outcome of the observed incCP is similar with symCP.
Circulating extracellular vesicles carrying Firmicutes can predict response to pembrolizumab in urothelial carcinoma
Authors: A. Kawashima, J. Kentaro, D. Motooka, A. Yamamoto, T. Uemura, G. Yamamichi, K. Okada, E. Tomiyama, Y. Koh, M. Matsushita, T. Kato, K. Hatano, M. Uemura, H. Wada, N. Nonomura
Journal: European Urology (2022)
MEDB-32. Reducing treatment-related toxicity for children with WNT-activated medulloblastoma
Authors: Jessica Taylor, Joseph Toker, Katherine Masih, Erica Nathan, Sabrina Terranova, Richard Gilbertson
Journal: Neuro-Oncology (2022)

Abstract WNT-medulloblastoma has an excellent prognosis, with an overall survival rate of 90% among children receiving standard-of-care (SOC) surgical resection, radiotherapy, and chemotherapy. Unfortunately, while curative, this treatment is associated with major, long-term, debilitating motor, developmental, and neuroendocrine side effects. Therefore, it is crucial we develop effective, less toxic therapies for these children. Similarities have been demonstrated between cancer cell lysosomes and those of patients with Niemann-Pick, a lysosomal storage disease characterised by lysosomal fragility and sphingomyelin accumulation. A class of drugs known as Functional Inhibitors of Acid Sphingomyelinase (FIASMAs), increase lysosomal sphingomyelin and destabilise the cancer cell’s more fragile lysosomal membrane which leads to the induction of cell-death pathways via lysosomal membrane permeabilisation. Loratadine, an antihistamine with high FIASMA activity, consistently induced lysosomal membrane permeabilisation, leading to increased cell-death, in our panel of mouse and human WNT-medulloblastoma lines. Loratadine exhibited no detrimental effect on normal mouse embryonic stem cells from the lower rhombic lip – the putative cell of origin in WNT-medulloblastoma. Luciferase-expressing mouse WNT-medulloblastoma cells were orthotopically implanted into CD1-nude mice and monitored for tumour development via bioluminescent imaging. Upon tumour engraftment, mice were subjected to reduced SOC (radiotherapy and adjuvant vincristine) plus a clinically relevant dose of loratadine. Response and survival were compared to mice treated with full SOC (radiotherapy, vincristine, cisplatin, and etoposide). Mice treated with 2mg/kg/day of loratadine following reduced SOC demonstrated increased survival when compared to those treated with full SOC (p=0.02) along with a significant reduction in weight loss during treatment (p=&amp;lt;0.0001). This work suggests that loratadine, or other FIASMA compounds, may be good alternative adjuvant therapies for WNT-medulloblastoma. Using less toxic adjuvants could improve long-term outcomes through reducing therapeutic related toxicities for children with this devastating disease.
Precision surgery for Von Hippel-Lindau renal cell carcinoma
Authors: A. Larcher, F. Belladelli, G. Fallara, I. Rowe, A. Ieva, M. Santangelo, R. Lucianò, C. Doglioni, C. Mattioli, M.T. Sciarrone Alibrandi, G. Guazzarotti, A. Damascelli, A. Bellin, D. Canibus, U. Capitanio, F. Montorsi, F. De Cobelli, R. Bertini, A. Salonia
Journal: European Urology (2022)
Patients surviving COVID-19 had increased risk for adverse mental health outcomes vs. persons without COVID-19
Authors: David King
Journal: Annals of Internal Medicine (2022)

ACP Journal ClubJune 2022Patients surviving COVID-19 had increased risk for adverse mental health outcomes vs. persons without COVID-19David King, MBBS, MPHDavid King, MBBS, MPHSchool of Medicine, University of Queensland, Brisbane, Queensland, Australia (D.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J22-0031 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationXie Y, Xu E, Al-Aly Z. Risks of mental health outcomes in people with covid-19: cohort study. BMJ. 2022;376:e068993. https://pubmed.ncbi.nlm.nih.gov/35172971Clinical Impact RatingsGIM/FP/GP: Mental Health: Hospitalists: References1. Vindegaard N, Benros ME. COVID-19 pandemic and mental health consequences: systematic review of the current evidence. Brain Behav Immun. 2020;89:531-42. [PMID: 32485289] Google Scholar2. Taquet M, Geddes JR, Husain M, et al. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021;8:416-27. [PMID: 33836148] Google Scholar3. Battle C, James K, Temblett P. Depression following critical illness: analysis of incidence and risk factors. J Intensive Care Soc. 2015;16:105-8. [PMID: 28979391] Google Scholar Author, Article, and Disclosure InformationAffiliations: School of Medicine, University of Queensland, Brisbane, Queensland, Australia (D.K.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J22-0031.This article was published at Annals.org on 7 June 2022.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6Page: JC69KeywordsAntidepressantsBrainCOVID-19Cohort studiesDisclosureDrugsHospitalizationsOpioidsPsychiatry and mental healthVeteran care ePublished: 7 June 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
TBIO-09. EZHIP is not expressed within the developing mouse or human brain
Authors: Subhi Talal Younes, Kristin Weaver, Anderson Collier, Betty Herrington
Journal: Neuro-Oncology (2022)

Abstract The protein EZHIP, first described as part of the genetic signature of group A posterior fossa ependymoma (PFA), functions in a manner analogous to the onco-histone H3K27M, itself first described in diffuse midline glioma (DMG). These two proteins modulate activity of the Polycomb repressive complex 2 (PRC2), resulting in global loss of H3K27 trimethylation. Thus, both PFA and DMG are characterized by global loss of the H3K27me3 mark, and PRC2 modulation is critical to oncogenesis of these tumors. However, the precise mechanism(s) of EZHIP and H3K27M-induced tumorigenesis is not known. One possibility is that EZHIP is expressed within the developing brain where it acts to modulate cellular development. In turn, EZHIP overexpression or H3K27M mutation could co-opt this developmental program to drive tumorigenesis. Relatedly, whether EZHIP is expressed in the cell of origin for PFA or DMG is not known. In order to evaluate these hypotheses, we defined the landscape of EZHIP expression in both murine and human developing brain. Leveraging single cell RNA sequencing databases, we show that EZHIP is not expressed within the developing mouse brain, a finding that is consistent across separate datasets. Similarly, EZHIP is not expressed in the developing murine cerebellum, where the cell of origin for PFA is located. Furthermore, we examined bulk RNA sequencing datasets of the developing human brain. Similar to our findings in the mouse brain, EZHIP is not expressed at any time point or spatial location within the developing human brain. Taken together, these data reject the above hypothesis, that EZHIP or H3K27M co-opt an endogenous PRC2 inhibitory developmental program. Similarly, these results show that EZHIP is not expressed within the cell of origin for PFA or DMG. Further studies will seek to understand the endogenous function of EZHIP by further defining its normal expression pattern and function.
Time at home among older adults with acute myeloid leukemia based on treatment intensity: A SEER-Medicare analysis.
Authors: Daniel R. Richardson, Xi Zhou, Christopher Edward Jensen, Katherine Elizabeth Reeder-Hayes, Jennifer Leigh Lund, Christopher Baggett
Journal: Journal of Clinical Oncology (2022)

6586 Background: Older adults with acute myeloid leukemia (AML) have identified time at home (TAH) as a critical outcome when deciding on treatment. No study to date has fully explored TAH for older adults with AML. Methods: We identified a cohort of adults age ≥66 years with a new diagnosis of AML from the SEER-Medicare linked database from 2004-2016. Individuals were stratified into high-intensity chemotherapy [HIC] v. hypomethylating agent [HMA] v. other using claims. The primary outcome was TAH, quantified by subtracting the total number of person-days spent in hospitals and skilled nursing facilities from the number of person-days survived. Demographics, comorbidities, frailty, and transfusion dependence were considered covariates. Results: 7,946 adults were included. 2,824 (36%) received HIC, 2,542 (32%) HMA, and 2,580 (33%) other. Mean age was 75 years (HIC: 73; HMA: 78; other: 76). The cohort was predominantly White (88%, Black 5%; Asian 3%; Hispanic 1%) and male (57%). Median survival was 7 months (HIC: 9; HMA: 8). Median total TAH was 151 days (Mean 426, Range 0-1825). Adults receiving HIC spent less time at home and more time hospitalized than those receiving HMAs each month in the first year (Table). Differences in TAH between HIC and HMA cohorts were most pronounced in the first 3 months (1 st : 49.5% v. 86.5%; 2 nd : 68.2% v. 84.1%; 3 rd : 77.3% v. 86.8%). Total TAH over 12 months was lower for those receiving HIC v. HMA (51.7% [187 days] v. 56.9% [205 days]). Transfusion dependence (≥ 1/month) was associated with decreased TAH at 1 month (OR 0.81, p&lt;0.001) and 12 months (OR 0.90, p=0.04). Other covariates were not associated with TAH. Conclusions: Although intensive chemotherapy resulted in slightly longer survival, older adults treated with HMAs had more time at home. Treatment decision-making should incorporate patient preferences for prolonging survival v. increasing time at home. The effect of new treatments (eg, venetoclax) on time at home should be evaluated in future studies. [Table: see text]